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ASH News Daily
http://www.hematology.org/Annual-Meeting/AND.aspx

Nov 7th, 2018 - ASH News Daily is the official print publication of the ASH annual meeting. View an archive of recent ASH News Daily publications

ASH 2018 coming attractions look at the big picture
https://www.mdedge.com/hematologynews/article/189383/aggressive-lymphomas/ash-2018-coming-attractions-look-big-picture

Nov 21st, 2018 - Big trials, big results in malignant and nonmalignant hematologic disorders are on the program at the 2018 ASH annual meeting.

What's Hot at This Year's ASH Meeting?
https://www.medscape.com/viewarticle/905521

Nov 23rd, 2018 - The premier event in hematology is celebrating its diamond anniversary. This will be the 60th annual meeting of the American Society of Hematology (ASH). It will be returning to the city of San Diego, California, and will run from November 30 to December 4.

Every Patient Tells a Story: Using Narrative Medicine to Cure Disease
https://www.ashclinicalnews.org/on-location/every-patient-tells-story-using-narrative-medicine-cure-disease/

Nov 21st, 2018 - As part of the Education Program at the 2018 ASH annual meeting, three physician-writers will offer their take on the intersection of storytelling, writing, and medicine – asking why doctors should care about the narrative, how the patient narrative informs treatment decisions, and how writing can be a tool for advocacy and change.

ASH-a-Palooza: Trainee Day. Reimagined
https://www.ashclinicalnews.org/on-location/ash-palooza-trainee-day-reimagined/

Nov 21st, 2018 - The “Trainee Day” that attendees may know from past annual meetings has been reimagined as ASH-a-Palooza – a new educational experience that will offer a relaxed, open learning environment for trainees in a festival-like setting with multiple opportunities for micro-learning. During breaks between sessions at Petco Park, trainees can enjoy ballpark-style food and are invited to visit informatio...

For the Love of the Lab: Interview with John E. Dick, PhD
https://www.ashclinicalnews.org/on-location/love-lab-interview-john-e-dick-phd/

Nov 21st, 2018 - John E. Dick, PhD, recipient of the 2018 Mentor Award in basic science, tells us about his career in the lab – from working at “the mecca of stem-cell research” to learning how to foster creativity in his own lab

Platelet Biogenesis in the Lung Circulation
http://www.bloodjournal.org/content/132/Suppl_1/SCI-22

Nov 21st, 2018 - Platelets are indispensable in hemostasis, thrombosis, and immune responses. In humans, billions of platelets are produced each day from megakaryocytes, however the mechanisms of mature platelet production are incompletely understood. Megakaryocytes are produced in the bone marrow and have been visualized to communicate with the bone marrow sinusoids to release proplatelet fragments. Megakaryoc...

Overall Survival of HIV-Positive Patients with HLH
http://www.bloodjournal.org/content/132/Suppl_1/4957

Nov 21st, 2018 - Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disorder affecting the interplay between natural killer cells, macrophages, and cytotoxic lymphocytes. In HLH, persistent macrophage activation results from dysregulated cytokines produced from T-lymphocytes. The disease can be primary (due to a genetic defect) or secondary (triggered by another disease proces...

Hemophagocytic Lymphohistiocytosis in Early Infancy- Pitfall of Differentiation between Hereditary and Infectious Reasons
http://www.bloodjournal.org/content/132/Suppl_1/4961

Nov 21st, 2018 - Hemophagocytic Lymphohistiocytosis (HLH) is characterized by pathologic immune activation which occurs either as a familial disorder or as an acquired condition. The diagnosis of HLH requires the presence of five out of nine criteria: fever, splenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis in bone marrow, hyperferritinemia, low or absent natural killer cell...

IL-6 As a Potential Cell Released Marker of Prostate Cancer Cell Death
http://www.bloodjournal.org/content/132/Suppl_1/4964

Nov 21st, 2018 - Introduction: Interleukin 6 (IL-6) is proinflammatory cytokine which is produced by cell when Nod-like receptors (NLRs) are activated. Increased production of IL-6 was shown to promote tumor growth and metastasis.Therefore, it could be suggested that activation of NLRs could support malignancy. PC-3, prostate tumor derived cells, was shown to produce IL-6; however, little is known about the rol...

5-Azacytidine Induces NOXA and PUMA Expression to Prime AML Cells for Venetoclax-Mediated Apoptosis
http://www.bloodjournal.org/content/132/Suppl_1/2644

Nov 21st, 2018 - Acute myeloid leukemia (AML) is a clonal hematologic malignancy characterized by genomic heterogeneity and epigenetic changes, including aberrant DNA hypermethylation. Phase-Ib clinical data in relapsed/refractory AML patients indicate that combining venetoclax with the hypomethylating agents (HMAs) 5-azacitidine (5-Aza) or decitabine results in an overall response (OR) of 62% (DiNardo et al. 2...

A 36-Dimensional Cytometry by Time of Flight (CyTOF) Analysis of De Novo Acute Myeloid Leukemia (AML) Patients Eligible for Intensive Chemotherapy
http://www.bloodjournal.org/content/132/Suppl_1/1502

Nov 21st, 2018 - Introduction Chemotherapy induced clonal selection and development are major contributors to disease relapse and resistance to therapy in AML. An immediate response to chemotherapy in intracellular signalling networks can be detected within minutes in vivo. (Irish J. et al 2004) We hypothesize that by analyzing the immediate intracellular chemotherapy response we might reveal which cancer clone...

A Feasibility and Safety Study of CD19 and CD22 Chimeric Antigen Receptors-Modified T Cell Cocktail for Therapy of B Cell Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/277

Nov 21st, 2018 - Introduction: Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has recently demonstrated high success but also shown limitations regarding their toxicity and development of CD19negative variants. Here we reported results from a phase I study designed to determine the safety of the CD19 CAR-T and CD22 CAR-T cocktail and the feasibility of making enough quantities to treat patients w...

A Genome-Wide CRISPR Screen Implicates MYC Dysregulation in TCF3-PBX1 B-ALL
http://www.bloodjournal.org/content/132/Suppl_1/3915

Nov 21st, 2018 - Introduction: Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer, of which, precursor B-cell ALL (B-ALL) accounts for approximately 80% of diagnoses. B-ALL is a heterogeneous disease, with patients characterised and risk stratified according to their cytogenetic profile. TCF3-PBX1 B-ALL was associated with a poor prognosis, but on current therapies outcome has greatly impr...

A Long-Term Retrospective Analysis of Arsenic-Containing Triple-Agents Treatment for Acute Promyelocytic Leukemia (APL) in a Cohort from a Single Hospital
http://www.bloodjournal.org/content/132/Suppl_1/4060

Nov 21st, 2018 - Objective: The long-term efficacy (June 2001 - May 2018) of newly diagnosed APL patients (pts) treated with either As4S4 or As2O3 in combination of all-trans retinoid acid (ATRA), and anthracycline-based chemotherapy in Lu Dao-Pei Hospital is analyzed. Methods: Firstly, 8 years from June 2001 to December 2009, a total of 88 newly diagnosed with APL patients were divided into two groups, who wer...

A Network Meta-Analysis of Clinical Trials Assessing Induction Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Among Young Adults
http://www.bloodjournal.org/content/132/Suppl_1/1432

Nov 21st, 2018 - Introduction: After establishing the diagnosis of acute myeloid leukemia (AML), remission induction chemotherapy is started with curative intent. Due to paucity of direct therapeutic comparison of induction regimens, relative efficacy of two drug standard regimens and three drug induction regimens among newly diagnosed young (<60 years) AML patients is not established. We conducted a systematic...

A Novel Predictor of Response to Gemtuzumab Ozogamicin Therapy in AML Provides Strategies for Sensitization of Leukemia Stem Cells in Individual Patients
http://www.bloodjournal.org/content/132/Suppl_1/2765

Nov 21st, 2018 - Acute myeloid leukemia (AML) patients with normal cytogenetics, NPM1 mutation, and no FLT3-ITD are considered to be at low molecular risk (LMR). We previously reported that most LMR patients have a low LSC17 score; these patients derive benefit from the addition of low fractionated doses of gemtuzumab ozogamicin (GO) to standard treatment and have favorable survival outcomes compared to patient...

A Novel Risk-Model to Predict Time to First Treatment (TTT) in Chronic Lymphocytic Leukemia Based on Heavy+Light Chain Immunoparesis and Serum Free Light Chain Analysis: Results from the Israeli CL...
http://www.bloodjournal.org/content/132/Suppl_1/1849

Nov 21st, 2018 - Introduction: Chronic Lymphocytic Leukemia (CLL) is frequently accompanied by immune dysregulation. Hypogammaglobulinemia is one of the most important immune defects encountered, and all three classes of immunoglobulins (IgG, A and M) can be involved. Recently, novel heavy+light chain (HLC) immunoassays have become available that quantify the light chain types of each immunoglobulin class (e.g....

A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML) - Interim Analysis of 1.5 µci/Kg/Dose
http://www.bloodjournal.org/content/132/Suppl_1/1457

Nov 21st, 2018 - Background: Older patients (pts) with AML unfit for intense induction chemotherapy have a poor prognosis with a 5 year survival of <10%. 225Ac-lintuzumab is composed of 225Ac linked to a humanized anti-CD33 monoclonal antibody. Data were previously presented on the initial 13 pts who received 2.0 µCi/kg/dose on Days 1 and 8 (ASH, 2017, Abstract 616). Although that dose resulted in a high respon...

A Phase I, First-in-Human Study Evaluating the Safety and Preliminary Antileukemia Activity of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in Patients with Relapsed/Refractory Acute M...
http://www.bloodjournal.org/content/132/Suppl_1/27

Nov 21st, 2018 - INTRODUCTION: Overexpression of CD123, the alpha subunit of the IL-3 receptor, in multiple hematological malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN), makes this antigen an attractive target for the development of new therapeutics. IMGN632 is a CD123-targeting antibody-drug conjugate comprising...

A Phase II Study of Dasatinib and Dexamethasone As Primary Therapy Followed By Transplantation for Adults with Newly Diagnosed Ph/BCR-ABL1-Positive Acute Lymphoblastic Leukemia (Ph+ ALL): Final Res...
http://www.bloodjournal.org/content/132/Suppl_1/309

Nov 21st, 2018 - Dasatinib with corticosteroid yields high complete remission (CR) rates in Ph+ ALL with minimal induction death. Optimal post-remission therapy is not known. We report a prospective study evaluating dasatinib/dexamethasone induction then consolidation with reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), autologous HCT (autoHCT), or chemotherapy alon...

A Phase II Trial of Nivolumab Combined with Ibrutinib for Patients with Richter Transformation
http://www.bloodjournal.org/content/132/Suppl_1/296

Nov 21st, 2018 - Background: Outcomes of patients (pts) with Richter transformation (RT) remain dismal with a median survival of less than 1 year with chemoimmunotherapy (CIT). Dysfunction of T cells, NK cells and other immune subsets is common in pts with CLL. Checkpoint blockade is an emerging treatment approach for pts with RT (Ding et al. Blood 2017; Younes et al. ASH 2017). Methods: We designed an investig...

A Refined Regimen for Maximally Eliminating Early Life-Threatening Complications for Patients with High-Risk Acute Promyelocytic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/3994

Nov 21st, 2018 - Life-threatening complications, such as severe bleeding and/or differentiation syndrome at admission and/or along with induction treatment, among high-risk patients with acute promyelocytic leukemia (APL) are a worldwide puzzle towards the cure of the disease. Taking the rationale that high WBC count, at least in part, may cause cytokine storm related symptoms, we designed this refined regimen ...

ABL Tyrosine Kinase Inhibitors (TKIs) Are Associated with Increased Rho-Associated Kinase (ROCK) Activity That May Contribute to Vascular Toxicity in Patients with Chronic Myeloid Leukemia (CML)
http://www.bloodjournal.org/content/132/Suppl_1/1739

Nov 21st, 2018 - Introduction The use of 2nd or 3rd generation ABL TKIs in patients with CML is associated with vascular toxicity, including peripheral arterial occlusive disease and cardiovascular and cerebrovascular events. However, Imatinib, a 1st generation TKI, has not been shown to increase risk of cardiovascular events (Douxfils J et al. JAMA Oncol 2016;2:625). Therefore, there is a need to identify risk...

Acalabrutinib in Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study
http://www.bloodjournal.org/content/132/Suppl_1/692

Nov 21st, 2018 - Background: Bruton tyrosine kinase (BTK) is a critical component of B-cell receptor signaling pathway and a validated therapeutic target for CLL. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor with minimal off-target activity that has been shown to have an overall response rate (ORR) of 95% (85% partial response [PR]; 10% PR with lymphocytosis [PRL]) after a median follow-u...

Activated CLL B Cells Variably Modulate microRNA-155 Levels in Naïve CD4+ T Cells, and the Direction and Magnitude of microRNA-155 Change Correlates with Th17 Levels and Clinical Course
http://www.bloodjournal.org/content/132/Suppl_1/4402

Nov 21st, 2018 - T-helper 17 (Th17) cells constitute a subset of T cells that characteristically secrete IL-17. In addition to their normal adaptive immune functions, Th17 cells also play roles in supporting dysfunctional immune responses found in autoimmunity and cancer. Several studies suggest that Th17 cells play a protective role in chronic lymphocytic leukemia (CLL). For example, CLL patients exhibit varie...

Activation of NF-Kappa B-p62-NRF2 Signaling Supports the Survival of CLL Cells That Express High Levels of ROR1
http://www.bloodjournal.org/content/132/Suppl_1/3122

Nov 21st, 2018 - Recent studies have linked the autophagy adaptor p62/SQSTM1 to tumorigenesis via NRF2 signaling. Increased accumulation p62 is associated with disease progression in many cancers, however its expression in CLL has yet to be investigated. Importantly, p62, encoded by the SQSTM1 gene, mRNA expression and protein accumulation is regulated by nuclear factor-kappa B (NF-κB), a key transcription fact...

Acute Myeloid Leukemia Expands Osteoprogenitor Rich Niche in the Bone Marrow but Resorbs Mature Bone Causing Osteopenia/Osteoporosis in Animal Models
http://www.bloodjournal.org/content/132/Suppl_1/86

Nov 21st, 2018 - Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancy that originates in the bone marrow (BM). Despite advances in the molecular characterization of AML, factors regulating its progression are still not known. Among several BM niches that support AML growth in the BM, the osteogenic niche has gained attention in recent years owing to its potential role in leukemoge...

Adherence to Tyrosine Kinase Inhibitor Affects Overall Survival in Adult Korean Chronic Myeloid Leukemia Patients; Based on the National Health Information Database
http://www.bloodjournal.org/content/132/Suppl_1/1745

Nov 21st, 2018 - Objectives We evaluated clinical characteristics including adherence and its effects on overall survival (OS) in Korean patients diagnosed with chronic myeloid leukemia (CML) using National Health Information Database "NHID". Methods This study included patients 15 and older who were diagnosed with Philadelphia chromosome positive CML (ICD code C921) from 2005 to 2013 and prescribed with tyrosi...

Adoptive T-Cell Therapy for Acute Lymphoblastic Leukemia Targeting Multiple Tumor Associated Antigens
http://www.bloodjournal.org/content/132/Suppl_1/2693

Nov 21st, 2018 - Background: Leukemic relapse remains the major cause of treatment failure in hematopoietic stem cell transplant (HSCT) recipients. While the infusion of donor lymphocytes to prevent and treat relapse has been clinically implemented this strategy does not provide durable remissions and carries the risk of life-threatening graft-versus-host disease (GVHD). More recently the adoptive transfer of T...

ALKBH5 Functions As an Oncogene in Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/3910

Nov 21st, 2018 - N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic messenger RNAs (mRNAs) has been shown to play important roles in diverse cellular and pathological processes (Deng X, et al. Cell Res. 2018;28:507-517). ALKBH5, recently identified as a m6A demethylase, was reported to promote tumorigenesis and proliferation in glioblastoma stem-like cells (GSCs) (Zhang, S. et al. C...

Allogeneic CAR-T Cell Therapy for Treatment of Relapse after Allo-HSCT in Patients with Refractory CML Lymphoid Blast Crisis: Significance of HLA Matched Donor/Patient Pair in the Safety/Efficacy o...
http://www.bloodjournal.org/content/132/Suppl_1/4275

Nov 21st, 2018 - Introduction: CD19-specific CAR-T cells have shown promise in the treatment of relapsed or refractory Ph+ ALL. It remains to be established whether allogeneic CAR-T cells have clinical activity in patients with relapsed CML lymphoid blast crisis with a history of allo-HSCT. Here we report our experience in two cases of allogeneic CAR-T cell therapy for treatment of relapse after allo-HSCT in pa...

AML with Mutations in IDH1 and DNMT3A Exhibits a Distinct Epigenetic Signature with Poorer Overall Survival
http://www.bloodjournal.org/content/132/Suppl_1/1471

Nov 21st, 2018 - Acute Myeloid Leukemia (AML) is a biologically diverse disease with subtypes that can be identified through integrated cytogenetic, mutational, and epigenetic characterization. Mutations in epigenetic regulators such as IDH1, IDH2, and DNMT3A are among the most common gene mutations found in AML (Cancer Genome Atlas Research et al. 2013; Papaemmanuil et al. 2016). Targeted inhibitors of IDH1 an...

AMV564, a Bivalent Bispecific (2×2) CD33/CD3 T-Cell Engager, Is Active and Improves Survival in a Mouse Model of Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/2727

Nov 21st, 2018 - Background: AMV564 is a novel bivalent, bispecific (2x2) CD33/CD3 targeted immunotherapy that binds both CD33 and the invariant CD3ε on T-cell receptors with strong avidity, thus creating an immune synapse between CD33-expressing cells and T cells, initiating T-cell directed lysis of CD33 expressing cells, and inducing expansion, differentiation and proliferation of T cells. AMV564 is being eva...

Anti-CD20 Monoclonal Antibodies Hijack the B-Cell Receptor Signaling Cascade Thereby Activating the NOTCH1 Signaling Pathway
http://www.bloodjournal.org/content/132/Suppl_1/588

Nov 21st, 2018 - NOTCH1 is a cell surface receptor, regulation of which depends on the integrity and subsequent cleavage of its inhibitory domain. Subtle mechanical forces transmitted after ligand-binding [Wang et al., 2013] or removal of Ca2+-ions [Rand et al., 2000] make the site accessible for cleavage, resulting in release of the transcription factor NICD1. Mutations in NOTCH1 that prolong NICD1 activity ha...

Anti-Human CD117 CAR T-Cells Efficiently Eliminate Hematopoietic Stem and CD117-Positive AML Cells
http://www.bloodjournal.org/content/132/Suppl_1/4063

Nov 21st, 2018 - Introduction: Acute Myeloid Leukemia (AML) is a clonal disease of the hematopoietic system that originates from immature hematopoietic stem and progenitor cells (HSPC). Because some AML-initiating cells are comparatively resistant to conventional cytotoxic agents, disease relapses are common with current treatment approaches. As an alternative, immunological eradication of leukemic cells by ado...

Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial
http://www.bloodjournal.org/content/132/Suppl_1/2680

Nov 21st, 2018 - Outcomes in elderly patients with acute myeloid leukemia (AML) are still adverse, as the majority does not qualify for intensive therapy or allogenic stem cell transplantation (ASCT). DNA hypomethylating agents (HMAs) induce remissions and prolong survival in a fraction of these patients. However, overall prognosis remains dismal and all patients progress due to therapy-resistant leukemia stem ...

AraC-Daunorubicin-Etoposide (ADE) Response Prediction in Pediatric AML Patients Using a Computational Biology Modeling (CBM) Based Precision Medicine Workflow
http://www.bloodjournal.org/content/132/Suppl_1/4034

Nov 21st, 2018 - Background: Pediatric AML (pAML) treatment outcomes can vary due to genomic heterogeneity. Thus, selecting the right drugs for a given patient is challenging. There is a need for a priori means of predicting treatment responses based on tumor "omics". Computational biology modeling (CBM) is a precision medicine approach by which biological pathways of tumorigenesis are mapped using mathematical...

Assessment of the Genomic Landscape of Intermediate Risk Acute Myeloid Leukemia As Defined By 2010 ELN Risk Classification
http://www.bloodjournal.org/content/132/Suppl_1/994

Nov 21st, 2018 - Background: In 2010 an international expert working group (European LeukemiaNet, ELN) has published recommendations for the diagnosis and management of acute myeloid leukemia (AML) including a risk stratification by cyto- and molecular genetics, subdividing AML into four risk groups. Emerging data on molecular markers in AML has led to an update of stratification criteria by ELN in 2017 includi...

Aurora Kinase a/MDM2-Mediated SETD2 Loss of Function in Chronic Myeloid Leukemia Patients in Blast Crisis Induces Genetic Instability and Can be Therapeutically Targeted
http://www.bloodjournal.org/content/132/Suppl_1/1726

Nov 21st, 2018 - The SETD2 protein is a histone methyltransferase that specifically catalyzes the trimethylation of Lysine 36 on histone H3 (H3K36me3). SETD2/H3K36me3 are implicated in transcript elongation and splicing, DNA repair, chromosome segregation. SETD2 gene deletions and/or mutations (mostly frameshift or nonsense) have been reported in solid tumors (clear cell renal cell carcinoma, bladder cancer, lu...

ATG2B/Gskip in De Novo Acute Myeloid Leukemia (AML): High Prevalence of Germline Predisposition in French West Indies and Potential Role of Overexpression in Acquired AML
http://www.bloodjournal.org/content/132/Suppl_1/1482

Nov 21st, 2018 - In 2015, a germline copy number variation of chromosome 14 (CNVdup14) including ATG2B and GSKIP genes was described as a predisposition genetic factor responsible of familial myeloproliferative neoplasms from French West Indies (Saliba et al, Nat Gen 2015), frequently progressing to AML. In this study, we looked at the presence of this CNVdup14 in a cohort of Caribbean islands patients (pts) wi...

BET Inhibitors Potentiate Activation of p53 and Killing of AML By MDM2 Inhibitors — a Candidate Combination Therapy
http://www.bloodjournal.org/content/132/Suppl_1/3912

Nov 21st, 2018 - In 2016, there will be approximately 19,950 new cases of Acute Myeloid Leukaemia (AML) in the United States. After diagnosis, five-year survival is currently ~26%, with available therapeutic approaches. Therefore, there remains a critical requirement for novel therapies for AML. Bromodomain and extra-terminal domain inhibitors (BETi) are emerging as exciting therapeutic agents for haematopoieti...

B-Cell Receptor Signaling Drives Glycolysis in Chronic Lymphocytic Leukemia Cells
http://www.bloodjournal.org/content/132/Suppl_1/3121

Nov 21st, 2018 - A key feature of tumor cell energetics is preferential metabolism of glucose to lactate even in the presence of oxygen (aerobic glycolysis). While this is an inefficient way of producing energy, it enables cancer cells to use glucose to generate biomass to support cellular proliferation. It is unclear whether this process is playing a role in the pathogenesis of chronic lymphocytic leukemia (CL...

Bone Marrow Hematopoietic Dysfunction in Untreated Chronic Lymphocytic Leukemia Is Partially Mediated By Exposure to Constituents of the Leukemic Microenvironment
http://www.bloodjournal.org/content/132/Suppl_1/3132

Nov 21st, 2018 - Peripheral immune dysfunction in B-Chronic Lymphocytic Leukemia (CLL) is well-studied and likely relates to the incidence of serious recurrent infections and second malignancies that plague CLL patients. However, the current paradigms of known immune abnormalities are not able to consistently explain these complications and it is not easy to correct CLL patient immune status. Here, we expand on...

Blinatumomab in Combination with Immune Checkpoint Inhibitors of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Preliminar...
http://www.bloodjournal.org/content/132/Suppl_1/557

Nov 21st, 2018 - Background: Blinatumomab, a CD19/CD3 bispecific T cell engager antibody construct, leads to improved outcomes in patients with R/R CD19+ ALL compared to standard chemotherapy. However, most adults fail to achieve complete remission (CR) with blinatumomab, and the median duration of remission is only 7.3 months. Preclinical studies have shown significantly increased PD-L1 expression on leukemic ...

BST-236, a Novel Cytarabine Prodrug, Is Safer and As Effective As Cytarabine in In Vivo Leukemia Models
http://www.bloodjournal.org/content/132/Suppl_1/1451

Nov 21st, 2018 - Introduction: Acute myeloid leukemia (AML) is associated with poor outcomes in older and medically unfit patients, largely due to the severe toxicity associated with cytarabine treatment, which precludes the administration of effective cytarabine doses. BST-236 is a prodrug of cytarabine, inactive in its prodrug form and designed to deliver cytarabine to leukemia cells with reduced systemic tox...

BRCA1/2 Containing Complex 3 (BRCC36) Is Recurrently Mutated in AML with t(8;21) and Associated with Increased Sensitivity to Chemotherapy through Impairment of the DNA Damage Repair Pathway
http://www.bloodjournal.org/content/132/Suppl_1/1487

Nov 21st, 2018 - Introduction BRCA1/BRCA2-containing complex 3 (BRCC36) is a Lys63-specific deubiquitinating enzyme (DUB) involved in DNA damage repair. Mutations in BRCC36 have been identified in 2-3% of patients with myelodysplastic syndromes (MDS) and secondary AML (sAML). The role of BRCC36 mutations in de novo AML and their impact on DNA damage-inducing cytotoxic chemotherapy sensitivity is not clear. Aim ...

Catecholamine Exposure Accelerates In Vivo Leukemogenesis in Acute Myeloid Leukemia Patient Derived Xenografts
http://www.bloodjournal.org/content/132/Suppl_1/1475

Nov 21st, 2018 - Mouse xenografts are routinely used for in vivo studies on human acute myeloid leukemia (AML) cells. However, a significant proportion of primary AML samples (~50-60% of cases) are not able to repopulate mice, or respectively require a particularly long time (up to 9 months) to show detectable engraftment in such models. Here we report that changing the transplantation time-point from day (5:00...

Cardiovascular Mortality Among CML Patients in the Pre-TKI and TKI Eras: A SEER Analysis 1992-2004
http://www.bloodjournal.org/content/132/Suppl_1/1737

Nov 21st, 2018 - Background: Since the US Food and Drug Administration (FDA) approved the first BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) imatinib in 2002 as the first line therapy1, chronic phase chronic myeloid leukemia (CML-CP), once a uniformly fatal disease, now has become a disease that is controlled in >90% patients2. Conventional treatment for CML before TKIs included hydroxyurea, interferon alp...

CD79a Is Associated with Central Nervous System Infiltration of Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/386

Nov 21st, 2018 - Despite the advances in the treatment of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), infiltration of the central nervous system (CNS) remains a clinical challenge. Certain cytogenetic subtypes such as E2A-PBX1-and BCR-ABL-positive BCP-ALL confer a higher risk for CNS involvement initially and for CNS relapse. Novel strategies to predict CNS and to eradicate leukemic cells...